Ling-Gong Zhao, Pei Li, Ying Dai
May 11, 2020
Citations
1
Influential Citations
11
Citations
Quality indicators
Journal
Journal of Cardiovascular Pharmacology
Abstract
Cardiac hypertrophy causes heart failure and is associated with hyperglycemia in patients with diabetes mellitus (DM). Mibefradil, which acts as a T-type calcium channel blocker, exerts beneficial effects in patients with heart failure. In this study, we explored the effects and mechanism of mibefradil on high glucose-induced cardiac hypertrophy in H9c2 cells. H9c2 cells were incubated in high-glucose medium and then treated with different concentrations of mibefradil in the presence or absence of the Akt inhibitor MK2206 or mTOR inhibitor rapamycin. Cell size was evaluated via immunofluorescence, and mRNA expression of cardiac hypertrophy markers (ANP, BNP, and β-MHC) was assessed by qRT-PCR. Changes in expression of p-PI3K, p-Akt, and p-mTOR were evaluated using western blotting, and autophagosome formation was detected by transmission electron microscopy. Our results indicate that mibefradil reduced the size of H9c2 cells, decreased mRNA expression of ANP, BNP, and β-MHC, and decreased the level of autophagic flux. However, MK2206 and rapamycin induced autophagy and reversed the effects of mibefradil in high-glucose-induced H9c2 cells. In conclusion, mibefradil ameliorated high-glucose-induced cardiac hypertrophy by activating the PI3K/Akt/mTOR pathway and inhibiting excessive autophagy. Our study suggests that mibefradil can be used therapeutically to ameliorate cardiac hypertrophy in patients with DM.